The long-range objective of this proposal is to identify the site(s) of synthesis and routes of clearance of the surfactant complex of the mammalian lung. Towards this end, studies will be conducted to develop a marker system for surfactant. An intimate relationship has been demonstrated between the appearance of surface activity, lamellar bodies, the alveolar lining layer and non-specific esterases. A variety of biochemical, cytochemical and electrophoretic techniques have been devised for the demonstration of non-specific esterases and will be used to test the invariability of this demonstrated correlation, i.e., to develop a marker system for the surfactant complex. Because of the established complexity of mammalian esterase systems, we propose to study a variety of inframammalian forms and compare them to a number of different mammals to find the most simple model system possible with regard to non-specific esterase activity and surface activity. The proposed phylogenetic survey of a variety of animals, utilizing the same techniques for each, should provide a meaningful base line for the appearance, location and nature of the surfactant complex. The effects of disease and experimental intervention on surfactant cannot be recognized, let alone understood, without such basic information.